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| | <StructureSection load='5bnr' size='340' side='right'caption='[[5bnr]], [[Resolution|resolution]] 1.89Å' scene=''> | | <StructureSection load='5bnr' size='340' side='right'caption='[[5bnr]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5bnr]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BNR OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BNR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5bnr]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BNR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BNR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4VL:1-{5-[2-FLUORO-5-(HYDROXYMETHYL)PHENYL]PYRIDIN-2-YL}PIPERIDINE-4-CARBOXYLIC+ACID'>4VL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4VL:1-{5-[2-FLUORO-5-(HYDROXYMETHYL)PHENYL]PYRIDIN-2-YL}PIPERIDINE-4-CARBOXYLIC+ACID'>4VL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5bnm|5bnm]], [[5bns|5bns]], [[5bqs|5bqs]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5bnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnr OCA], [https://pdbe.org/5bnr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bnr RCSB], [https://www.ebi.ac.uk/pdbsum/5bnr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnr ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabH, b1091, JW1077 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_III Beta-ketoacyl-[acyl-carrier-protein] synthase III], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.180 2.3.1.180] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5bnr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bnr OCA], [http://pdbe.org/5bnr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5bnr RCSB], [http://www.ebi.ac.uk/pdbsum/5bnr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5bnr ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FABH_ECOLI FABH_ECOLI]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain.[HAMAP-Rule:MF_01815] | + | [https://www.uniprot.org/uniprot/FABH_ECOLI FABH_ECOLI] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain.[HAMAP-Rule:MF_01815] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kazmirski, S L]] | + | [[Category: Kazmirski SL]] |
| - | [[Category: McKinney, D C]] | + | [[Category: McKinney DC]] |
| - | [[Category: Anti-bacterial]]
| + | |
| - | [[Category: Fabh]]
| + | |
| - | [[Category: Fatty acid synthesis]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
FABH_ECOLI Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for acetyl-CoA. Its substrate specificity determines the biosynthesis of straight-chain of fatty acids instead of branched-chain.[HAMAP-Rule:MF_01815]
Publication Abstract from PubMed
Fatty acid biosynthesis is essential to bacterial growth in Gram-negative pathogens. Several small molecules identified through a combination of high-throughput and fragment screening were cocrystallized with FabH (beta-ketoacyl-acyl carrier protein synthase III) from Escherichia coli and Streptococcus pneumoniae. Structure-based drug design was used to merge several scaffolds to provide a new class of inhibitors. After optimization for Gram-negative enzyme inhibitory potency, several compounds demonstrated antimicrobial activity against an efflux-negative strain of Haemophilus influenzae. Mutants resistant to these compounds had mutations in the FabH gene near the catalytic triad, validating FabH as a target for antimicrobial drug discovery.
Antibacterial FabH Inhibitors with Mode of Action Validated in Haemophilus influenzae by in Vitro Resistance Mutation Mapping.,McKinney DC, Eyermann CJ, Gu RF, Hu J, Kazmirski SL, Lahiri SD, McKenzie AR, Shapiro AB, Breault G ACS Infect Dis. 2016 Jul 8;2(7):456-64. doi: 10.1021/acsinfecdis.6b00053. Epub, 2016 May 9. PMID:27626097[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McKinney DC, Eyermann CJ, Gu RF, Hu J, Kazmirski SL, Lahiri SD, McKenzie AR, Shapiro AB, Breault G. Antibacterial FabH Inhibitors with Mode of Action Validated in Haemophilus influenzae by in Vitro Resistance Mutation Mapping. ACS Infect Dis. 2016 Jul 8;2(7):456-64. doi: 10.1021/acsinfecdis.6b00053. Epub, 2016 May 9. PMID:27626097 doi:http://dx.doi.org/10.1021/acsinfecdis.6b00053
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